The brain is a major target for oxidative stress because tissues contain high levels of unsaturated fatty acids, as well as increased mitochondria, which work for neuronal processing, energy production, and information transmission. Therefore, scientists, clinicians, and researchers alike are now looking at α-lipoic acid (ALA) as a potential therapeutic to prevent, or even slightly decrease, the symptoms of neurodegenerative diseases, such as Alzheimer’s, schizophrenia, and dementia. Some research also indicates that ALA, within omega 3 polyunsaturated fatty acid (PUFA) supplementation, can be used for major depressive disorder (MDD), and in post-stroke patients, particularly those suffering from depression (Blondeau, 2548, Klugman, 2).
ALA, previously known as thioctic acid, or more formally, 1,2-dithiolane-3 pentanoic acid, is a major endogenous fatty acid antioxidant that has the capacity to cross the blood brain barrier, a highly selective membrane. The antioxidant component of the molecule is contained within the sulfur group, which can accept or donate extra electrons, and is involved in many biochemical processes within the cell, particularly the mitochondria (Klugman, 3).
Important cofactors to the regeneration of oxidative and reductive ALA include: Vitamin C, Vitamin E, and other antioxdants. ALA has even been classified as having reductive/oxidative capabilities to that of glutathione (GSH) within the body (Seybolt, page 572). A beneficial therapeutic effect of ALA is the ability to raise intracellular GSH, nicotinamide adenine dinucleotide (NAD), and CoQ10 levels, which are also able to further increase antioxidant capacities. Chelation is tied with ALA, since this PUFA is able to form stable complexes with zinc, copper, and manganese, to act to remove potential reactive oxidant species (Klugman, 3).
The pathogenesis of Alzheimer’s disease (AD) includes extensive lipid peroxidation, iron deposition, and formation of neurofibrillary tangles, composed of beta-amyloid sheets, which significantly disrupt neural connections and memory formation. Few rat studies have shown that ALA therapy can partially restore memory loss, as well as improve long-term memory in aging rats, by means of mitochondrial protection from oxidative stress. Based on animal studies, ALA is a beneficial treatment approach to Alzheimer’s neurodegeneration. However, due to a lack of double-blind placebo-controlled human studies, data is inconclusive and no particular therapeutic dose has been determined for AD (Klugman, 4).
Schizophrenia affects about 1% of the general population, with increased incidences associated with first and second-degree relatives. Schizophrenia, a highly multifactorial disease, can be partially attributed to increased oxidative stress, overabundance of reactive oxidative species, mitochondrial damage, lowered PUFAs, deficient electron transport chain (ETC) mechanisms (Complex I), lowered CoQ10, lowered GSH levels, or lowered synaptic transmission. Since few human studies have explored ALA supplementation for schizophrenia, Seybolt hypothesizes that co-administration of ALA with nicotinamide may alleviate signs and symptoms of schizophrenia through correction of mitochondrial dysfunction: increasing GSH levels, improving function and electron donation to Complex I of the ETC, and increasing NAD and anti-odixative capacities (Seybalt, 572-575).
In Blondeau’s study, ALA administration significantly reduced and prevented extensive ischemic brain damage and depression in post-stroke lab rats. The researchers postulated that ALA promoted neuronal plasticity with upregulation of sypaptophysin-1, VAMP-2, SNAP-25, and V-GLUT. These elements are involved with synaptogenesis and neuronal transmission of serotonin, dopamine, and norepinephrine, as well as other neurotransmitters. Although depression is a highly mulitfactorial disorder, increasing neural plasticity can be an important therapeutic target (Blondeau).
In rat studies, ALA administration, and other omega 3 PUFAs, have been shown to increase brain-derived neurotrophic factor (BDNF) by at least 50% in the hippocampus and cortex. BDNF is typically secreted by neuronal stem cells, and pathways are mainly involved in neurogenesis, cell survival, neuronal plasticity, and neuroprotection. This neurotrophic factor has also shown to clinically have anti-depressant activity in lab rats, leading researchers to conclude that therapeutic doses of ALA would have similar anti-depressant effects in humans suffering from MDD or post-stroke depression (Blondeau, 2549, Klugman, 5).
Although there have been limited human studies on appropriate dosage of ALA in treatment of psychiatric disorders, general oral and intravenous dosage of ALA range from 300mg to 1800mg per day. There have been no contraindications determined in administration at this dosage, with poorly documented effects in pregnant women, side effects, toxicities, and other drug, vitamin, or herb interactions (“Alpha Lipoic Acid”, page 1).
Although ALA was not directly attributed to other psychiatric diseases in particular, it is important to remember that omega 3 polyunsaturated fatty acids are important in neuronal health and may be used as a supplemental therapeutic in other disorders such as bipolar disorder, mania, cognitive impairments, and attention deficit hyperactivity disorder. ALA primarily works through anti-oxidative mechanisms to enhance mitochondrial functioning, enhance action potential conduction and neuronal transmission, induce neuroprotectve effects, and help with neuronal plasticity of both hippocampal and cortical centers in the brain. Although most studies have concentrated on lab rats, few studies have been on humans concerning ALA supplementation with neuropsychiatric conditions, only indicating that future studies are needed for appropriate levels of supplementation for neuroprotection and treatment.
Works Cited
“Alpha Lipoic Acid (ALA) Information from Drugs.com.” Drugs.com. Wolters Kluwer Health, 2009. Web. 27 Aug 2011. .
Blondeau, N, et. al. “Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke.” Neuropsychopharmacology. 34. (2009): 2548-2559. Print.
Klugman, A, J Sauer, N Tabet, and R Howard. “Alpha lipoic acid for dementia (Review).” Cochrane Library. 4 (2008): 1-12. Print.
Seybolt, Sheila. “Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?” Medical Hypotheses. 75. (2010): 572-575. Print.
The brain is a major target for oxidative stress because tissues contain high levels of unsaturated fatty acids, as well as increased mitochondria, which work for neuronal processing, energy production, and information transmission. Therefore, scientists, clinicians, and researchers alike are now looking at α-lipoic acid (ALA) as a potential therapeutic to prevent, or even slightly decrease, the symptoms of neurodegenerative diseases, such as Alzheimer’s, schizophrenia, and dementia. Some research also indicates that ALA, within omega 3 polyunsaturated fatty acid (PUFA) supplementation, can be used for major depressive disorder (MDD), and in post-stroke patients, particularly those suffering from depression (Blondeau, 2548, Klugman, 2).
ALA, previously known as thioctic acid, or more formally, 1,2-dithiolane-3 pentanoic acid, is a major endogenous fatty acid antioxidant that has the capacity to cross the blood brain barrier, a highly selective membrane. The antioxidant component of the molecule is contained within the sulfur group, which can accept or donate extra electrons, and is involved in many biochemical processes within the cell, particularly the mitochondria (Klugman, 3).
Important cofactors to the regeneration of oxidative and reductive ALA include: Vitamin C, Vitamin E, and other antioxdants. ALA has even been classified as having reductive/oxidative capabilities to that of glutathione (GSH) within the body (Seybolt, page 572). A beneficial therapeutic effect of ALA is the ability to raise intracellular GSH, nicotinamide adenine dinucleotide (NAD), and CoQ10 levels, which are also able to further increase antioxidant capacities. Chelation is tied with ALA, since this PUFA is able to form stable complexes with zinc, copper, and manganese, to act to remove potential reactive oxidant species (Klugman, 3).
The pathogenesis of Alzheimer’s disease (AD) includes extensive lipid peroxidation, iron deposition, and formation of neurofibrillary tangles, composed of beta-amyloid sheets, which significantly disrupt neural connections and memory formation. Few rat studies have shown that ALA therapy can partially restore memory loss, as well as improve long-term memory in aging rats, by means of mitochondrial protection from oxidative stress. Based on animal studies, ALA is a beneficial treatment approach to Alzheimer’s neurodegeneration. However, due to a lack of double-blind placebo-controlled human studies, data is inconclusive and no particular therapeutic dose has been determined for AD (Klugman, 4).
Schizophrenia affects about 1% of the general population, with increased incidences associated with first and second-degree relatives. Schizophrenia, a highly multifactorial disease, can be partially attributed to increased oxidative stress, overabundance of reactive oxidative species, mitochondrial damage, lowered PUFAs, deficient electron transport chain (ETC) mechanisms (Complex I), lowered CoQ10, lowered GSH levels, or lowered synaptic transmission. Since few human studies have explored ALA supplementation for schizophrenia, Seybolt hypothesizes that co-administration of ALA with nicotinamide may alleviate signs and symptoms of schizophrenia through correction of mitochondrial dysfunction: increasing GSH levels, improving function and electron donation to Complex I of the ETC, and increasing NAD and anti-odixative capacities (Seybalt, 572-575).
In Blondeau’s study, ALA administration significantly reduced and prevented extensive ischemic brain damage and depression in post-stroke lab rats. The researchers postulated that ALA promoted neuronal plasticity with upregulation of sypaptophysin-1, VAMP-2, SNAP-25, and V-GLUT. These elements are involved with synaptogenesis and neuronal transmission of serotonin, dopamine, and norepinephrine, as well as other neurotransmitters. Although depression is a highly mulitfactorial disorder, increasing neural plasticity can be an important therapeutic target (Blondeau).
In rat studies, ALA administration, and other omega 3 PUFAs, have been shown to increase brain-derived neurotrophic factor (BDNF) by at least 50% in the hippocampus and cortex. BDNF is typically secreted by neuronal stem cells, and pathways are mainly involved in neurogenesis, cell survival, neuronal plasticity, and neuroprotection. This neurotrophic factor has also shown to clinically have anti-depressant activity in lab rats, leading researchers to conclude that therapeutic doses of ALA would have similar anti-depressant effects in humans suffering from MDD or post-stroke depression (Blondeau, 2549, Klugman, 5).
Although there have been limited human studies on appropriate dosage of ALA in treatment of psychiatric disorders, general oral and intravenous dosage of ALA range from 300mg to 1800mg per day. There have been no contraindications determined in administration at this dosage, with poorly documented effects in pregnant women, side effects, toxicities, and other drug, vitamin, or herb interactions (“Alpha Lipoic Acid”, page 1).
Although ALA was not directly attributed to other psychiatric diseases in particular, it is important to remember that omega 3 polyunsaturated fatty acids are important in neuronal health and may be used as a supplemental therapeutic in other disorders such as bipolar disorder, mania, cognitive impairments, and attention deficit hyperactivity disorder. ALA primarily works through anti-oxidative mechanisms to enhance mitochondrial functioning, enhance action potential conduction and neuronal transmission, induce neuroprotectve effects, and help with neuronal plasticity of both hippocampal and cortical centers in the brain. Although most studies have concentrated on lab rats, few studies have been on humans concerning ALA supplementation with neuropsychiatric conditions, only indicating that future studies are needed for appropriate levels of supplementation for neuroprotection and treatment.
Works Cited.
“Alpha Lipoic Acid (ALA) Information from Drugs.com.” Drugs.com. Wolters Kluwer Health, 2009. Web. 27 Aug 2011.
Blondeau, N, et. al. “Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke.” Neuropsychopharmacology. 34. (2009): 2548-2559. Print.
Klugman, A, J Sauer, N Tabet, and R Howard. “Alpha lipoic acid for dementia (Review).” Cochrane Library. 4 (2008): 1-12. Print.
Seybolt, Sheila. “Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?” Medical Hypotheses. 75. (2010): 572-575. Print.